Nerve growth factor (NGF) is present in the central nervous system and has specific, neurotrophic effects on cholinergic neurons of the basal forebrain which are known to degenerate during Alzheimer's disease. To understand the regulation of NGF expression in the brain, we are interested in detaining whether glial cells or neurons that communicate with cholinergic neurons, or both, produce NGF. The proposed work is based on the finding that a number of cell types and tissues that produce NGF in vivo produce greatly elevated levels of NGF in vitro. This allowed the detection of NGF produced by the iris, heart and sciatic nerve before techniques were developed that were sensitive enough to detect NGF produced by these sources in vivo. Glial cells have recently been shown to produce elevated levels of NGF in culture compared to the levels of NGF normally found in the brain. The proposed study will characterize the expression of NGF in glial and neuronal cells cultured from the brain to develop their relationship to normal NGF expression in the brain. This will lead to a better understanding of which cell types produce NGF and how the regulation of NGF expression by these cells will be modulated, ultimately for therapeutic purposes.